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Alkermes Initiates Clinical Study of ALKS 4230 Administered Subcutaneously in Patients With Advanced Solid Tumors

On February 26, 2019 Alkermes plc (Nasdaq: ALKS) reported the initiation of ARTISTRY-2, a new clinical study of ALKS 4230 administered subcutaneously as monotherapy and in combination with the PD-1 inhibitor KEYTRUDA (pembrolizumab) in patients with advanced solid tumors (Press release, Alkermes, FEB 26, 2019, View Source;p=irol-newsArticle&ID=2388952 [SID1234533688]). The study will explore the safety, tolerability and efficacy of ALKS 4230 administered subcutaneously and assess once-weekly and once-every-three-week dosing schedules. ALKS 4230 is a novel, engineered fusion protein designed to selectively activate tumor-killing immune cells while avoiding the expansion of immunosuppressive cells by preferentially binding to the intermediate-affinity interleukin-2 (IL-2) receptor complex. Pembrolizumab is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells.

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ARTISTRY-2, a phase 1/2 study, will be conducted in two stages: dose-escalation followed by dose-expansion. The dose-escalation stage is designed to evaluate the safety and tolerability of ascending doses of ALKS 4230 administered subcutaneously once-weekly and once-every-three-weeks as both lead-in monotherapy and in combination with pembrolizumab. Following identification of the optimal dose and recommended dosing schedule, the dose-expansion stage of the study will evaluate ALKS 4230 administered subcutaneously in combination with pembrolizumab in patients with advanced solid tumors. The dose-expansion stage will evaluate overall response rate, duration of response, non-progression rate at specific time points and overall survival.

"The initiation of our clinical subcutaneous dosing study represents an important milestone for the ALKS 4230 program as we explore new regimens that may offer patients a more convenient alternative to daily IV dosing that is complementary to checkpoint inhibitor regimens," said Craig Hopkinson, M.D., Chief Medical Officer and Senior Vice President of Medicines Development and Medical Affairs at Alkermes. "Based on the emerging profile of ALKS 4230, we’ve rapidly expanded our clinical development program in recent months to evaluate combination therapy, potential efficacy in new tumor types and dosing optionality. The expansion of this program reflects our belief in the significant potential of ALKS 4230 and our recognition of the urgent and persistent need that exists for patients with cancer."

Data presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 33rd Annual Meeting demonstrated that subcutaneous administration of ALKS 4230 in non-clinical models achieved similar total systemic exposure of ALKS 4230 compared to intravenous (IV) administration, yet with less frequent dosing and a lower Cmax, leading to similar expansion of total CD8+ T cell and natural killer (NK) cell populations. These data support further clinical evaluation of subcutaneous administration of ALKS 4230 as an alternative to IV dosing.

About ALKS 4230
ALKS 4230 is a novel, engineered fusion protein designed to selectively activate tumor-killing immune cells while avoiding the expansion of immunosuppressive cells by preferentially binding to the intermediate-affinity interleukin-2 (IL-2) receptor complex. The selectivity of ALKS 4230 is designed to leverage the proven anti-tumor effects of existing IL-2 therapy while mitigating certain limitations.

About the ARTISTRY Clinical Program
ARTISTRY is an Alkermes-sponsored clinical program evaluating ALKS 4230 in patients with advanced solid tumors. ARTISTRY-1 is an ongoing phase 1 study in which ALKS 4230 is administered as an intravenous infusion daily for five consecutive days. ARTISTRY-1 has three distinct stages: an ongoing monotherapy dose-escalation stage, a planned monotherapy dose-expansion stage and an ongoing combination therapy stage with pembrolizumab. ARTISTRY-2 is the second clinical study to initiate in the ARTISTRY clinical development program for ALKS 4230.

Omeros Corporation to Announce Fourth Quarter and Year-End 2018 Financial Results on March 1, 2019

On February 26, 2019 Omeros Corporation (NASDAQ: OMER), reported that the company will issue its fourth quarter and year-end 2018 financial results for the period ended December 31, 2018, on Friday, March 1, 2019, before the market opens (Press release, Omeros, FEB 26, 2019, View Source [SID1234533687]). Omeros management will host a conference call and webcast that day at 8:30 a.m. Eastern Time (5:30 a.m. Pacific Time) to discuss the financial results.

Conference Call Details

To access the live conference call via phone, please dial (844) 831-4029 from the United States and Canada or (920) 663-6278 internationally. The participant passcode is 3544038. Please dial in approximately 10 minutes prior to the start of the call. A telephone replay will be available for one week following the call and may be accessed by dialing (855) 859-2056 from the United States and Canada or (404) 537-3406 internationally. The replay passcode is 3544038.

To access the live or subsequently archived webcast of the conference call on the internet, go to the company’s website at www.omeros.com and select "Events" under the Investors section of the website. To access the live webcast, please connect to the website at least 15 minutes prior to the call to allow for any software download that may be necessary.

Verastem Oncology to Announce Fourth Quarter and Full-Year 2018 Financial Results and Corporate Update on March 12, 2019

On February 26, 2019 Verastem, Inc. (Nasdaq:VSTM) (Verastem Oncology or the Company), a biopharmaceutical company focused on developing and commercializing medicines seeking to improve the survival and quality of life of cancer patients, reported that the Company will host a conference call and webcast on Tuesday, March 12, 2019 at 4:30 p.m. Eastern Time to discuss corporate updates and financial results for the fourth quarter and year ended December 31, 2018 (Press release, Verastem, FEB 26, 2019, View Source;p=irol-newsArticle&ID=2388942 [SID1234533686]).

The call can be accessed by dialing (877) 341-5660 (U.S. and Canada) or (315) 625-3226 (international), five minutes prior to the start of the call and providing the passcode 2849017. The live, listen-only webcast of the conference call can be accessed by visiting the investors section of the Company’s website at www.verastem.com. A replay of the webcast will be archived on the Company’s website for 90 days following the call.

Lynparza significantly delayed disease progression as 1st-line maintenance treatment in germline BRCA-mutated metastatic pancreatic cancer

On February 26, 2019 AstraZeneca and MSD Inc., Kenilworth, N.J., US (MSD: known as Merck & Co., Inc. inside the US and Canada) reported positive results from the Phase III POLO trial (Press release, AstraZeneca, FEB 26, 2019, View Source [SID1234533685]).

Results from the trial showed a statistically-significant and clinically-meaningful improvement in progression-free survival (PFS) with Lynparza (olaparib) vs. placebo. The safety and tolerability profile of Lynparza was consistent with previous trials.

POLO is a randomised, double-blinded, placebo-controlled trial exploring the efficacy of Lynparza tablets as 1st-line maintenance monotherapy in patients with germline BRCA-mutated (gBRCAm) metastatic adenocarcinoma of the pancreas (pancreatic cancer) whose disease has not progressed on platinum-based chemotherapy.

José Baselga, Executive Vice President, Research and Development, Oncology, said: "This is the first positive Phase III trial of any PARP inhibitor in germline BRCA-mutated metastatic pancreatic cancer, a devastating disease with critical unmet need. The results of POLO provide further evidence of the clinical benefit of Lynparza across a variety of BRCA-mutated tumour types. We will discuss these results with global health authorities as soon as possible."

Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said: "Trials like POLO demonstrate the shared commitment of MSD and AstraZeneca to assess treatments for difficult-to-treat cancers. The clinically-meaningful results of this trial potentially support the value of testing for germline BRCA mutations in patients with metastatic pancreatic cancer."

AstraZeneca and MSD plan to present the full data from the trial at a forthcoming medical meeting.

About POLO

POLO is a Phase III randomised, double-blinded, placebo-controlled, multicentre trial of Lynparza tablets (300mg twice daily) as maintenance monotherapy vs. placebo. The trial randomised 154 patients with gBRCAm metastatic pancreatic cancer whose disease had not progressed on 1st-line platinum-based chemotherapy. Patients were randomised (3:2) to receive Lynparza or placebo until disease progression. The primary endpoint was PFS and key secondary endpoints included overall survival, time to second disease progression, overall response rate, disease control rate and health-related quality of life.

About Lynparza

Lynparza (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response in cells/tumours harbouring a deficiency in homologous recombination repair (HRR), such as mutations in BRCA1 and/or BRCA2. Inhibition of PARP with Lynparza leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. Lynparza is being tested in a range of PARP-dependent tumour types with defects and dependencies in the DDR.

Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, is approved for multiple indications in advanced ovarian cancer and metastatic breast cancer and has been used in over 20,000 patients worldwide. Lynparza has the broadest and most advanced clinical trial development programme of any PARP inhibitor, and AstraZeneca and MSD are working together to understand how it may affect multiple PARP-dependent tumours as a monotherapy and in combination across multiple cancer types. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.

About pancreatic cancer

Pancreatic cancer is the 12th most common cancer worldwide,1 with 466,000 new cases in 2018 alone.1 Germline BRCA-mutated pancreatic cancer accounts for five to seven percent of all cases globally.2 With the worst survival rate of the most common cancers,3 it is the 4th leading cause of cancer death,4 and less than seven percent of patients survive more than five years after diagnosis.3 Early diagnosis of pancreatic cancer is difficult, as often there are no symptoms until it is too late.5 Around 80% of patients are diagnosed at the metastatic stage.6

About BRCA mutations

BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA and play an important role in maintaining the genetic stability of cells. When either of these genes is mutated, or altered, such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly, and cells become unstable. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer.

About the AstraZeneca and MSD strategic oncology collaboration

In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the United States and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialise Lynparza, the world’s first PARP inhibitor, and potential new medicine selumetinib, a MEK inhibitor, for multiple cancer types. Working together, the companies will develop Lynparza and selumetinib in combination with other potential new medicines and as monotherapies. Independently, the companies will develop Lynparza and selumetinib in combination with their respective PD-L1 and PD-1 medicines.

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance Oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

MEDIGENE ANNOUNCES DOSING OF FIRST PATIENT IN PHASE I/II TRIAL WITH TCR THERAPY MDG1011 FOR VARIOUS BLOOD CANCERS

On February 26, 2019 Medigene AG (FSE: MDG1, Prime Standard, SDAX), a clinical stage immuno-oncology company focusing on the development of T cell immunotherapies, reported that it has dosed the first patient in its first-in-human clinical trial with its TCR therapy candidate MDG1011 (Press release, MediGene, FEB 26, 2019, View Source [SID1234533684]). The Phase I/II trial investigates the safety and feasibility of MDG1011 for the treatment of various types of blood cancer, including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and multiple myeloma (MM). MDG1011 is a novel immunotherapy candidate using patient-derived, T cell receptor (TCR)-modified T cells targeting the tumor antigen PRAME (PReferentially expressed Antigen in MElanoma) and was administered for the first time to a multiple myeloma patient in the Department of Medicine 5 (Director Prof. Dr. Andreas Mackensen) at the Universitätsklinikum Erlangen, Germany. MDG1011 is designed as a one-time treatment.

Dr. Kai Pinkernell, CMO/CDO of Medigene, comments: "Hematologic cancers such as AML, MDS and MM in advanced stages are difficult to treat and usually associated with a very poor prognosis for patients. With our TCR therapy, we hope to open new treatment options for seriously ill patients and the first-time use on patients is a very important step in the development of this new therapeutic candidate."

In the Phase I portion of the trial, approximately 12 patients who are suffering from advanced stage AML, MDS and MM and have previously undergone several cycles of standard therapies will be treated with MDG1011. PRAME expression on the tumor cells as well as the blood serotype HLA-A * 02:01 are further inclusion criteria for patients who can participate in this multicenter, open-label, dose escalation study using a 3 + 3 design. Three dose cohorts and an optional fourth dose cohort will test dose ranges from 100,000 to 10,000,000 transduced T cells per kg of body weight. Each dose cohort consists of 3 patients. At least one MM patient and at least one AML or MDS patient need to be included in each cohort. Patients will undergo preconditioning treatment with cyclophosphamide and fludarabine. After completing treatment of all patients in a dose cohort and a four-week safety follow-up period, dose escalation will be determined by an independent Data and Safety Monitoring Board (DSMB). The primary endpoint for the Phase I portion of this clinical trial will be safety and feasibility at three months with a total follow-up period of up to 12 months. Several secondary endpoints (i.e. overall response rate (ORR)) will be assessed as well.

In the Phase II portion of the trial, presumably two of the three indications will be carried forward after a positive DSMB assessment regarding the safety of MDG1011 and review by the competent authority and central ethics committee. In the Phase II portion, 40 HLA-A*02:01 and PRAME positive patients will be treated with MDG1011; another 40 patients, who are positive for PRAME but negative for HLA-A*02:01, will be included in the control groups (20 treated and 20 control patients per indication) and treated with investigator choice therapy. Co-primary endpoints of the Phase II portion are safety and preliminary efficacy, where efficacy is measured as ORR at 3 months. Several secondary endpoints will be assessed here as well.

The clinical trial is being conducted by the Department of Internal Medicine III of the University Hospital Regensburg (Director: Prof. Dr. Wolfgang Herr) under the leadership of the coordinating investigator PD Dr. Simone Thomas, as well as by the University Hospitals of Erlangen and Würzburg, Germany. Up to five additional clinical centers in Germany are currently being opened and are anticipated to open recruitment within the next three to five months and screen additional patients for their suitability to participate in the study.

About Medigene’s TCR therapy: The TCR-T cell technology aims at arming the patient’s own T cells with tumor-specific T cell receptors. The receptor-modified T cells are then able to detect and efficiently kill tumor cells. This immunotherapy approach attempts to overcome the patient’s tolerance towards cancer cells and tumor-induced immunosuppression by activating and modifying the patient’s T cells outside the body (ex vivo). TCR-T therapy is developed to utilize a higher number of potential tumor antigens than other T cell-based immunotherapies, such as chimeric antigen receptor T cell (CAR-T) therapy. Medigene is establishing a pipeline of recombinant T cell receptors and has a collaboration with bluebird bio, Inc. for the development of six TCR-Ts.

About acute myeloid leukemia (AML): AML is a malignant disease of the hematopoietic system. The cause of the disease is the uncontrolled growth of nonfunctioning hematopoietic progenitor cells in the bone marrow. Typical symptoms of AML are anemia, fever, increased susceptibility to infection and bleeding. The disease develops rapidly and, if left untreated, can lead to death within a few weeks or months. AML therapy is usually started with intensive chemotherapy, often followed by consolidation therapy, with or without allogeneic hematopoietic stem cell transplantation. In a significant number of patients, relapse of the disease is expected.

About multiple myeloma (MM): Multiple myeloma (MM) is a malignant disease characterized by monoclonal plasma cell proliferation in the bone marrow, with increased production of complete or incomplete monoclonal immunoglobulins. These proteins are detectable in serum and / or urine. Every year around 3,000 men and about 2,700 women in Germany develop multiple myeloma. MM is thus the third most frequent hematological neoplasia after leukemia and non-Hodgkin’s lymphoma and responsible for about 1% of all cancers in Germany.

About myelodysplastic syndrome (MDS): The term myelodysplastic syndrome is a group of diseases of the bone marrow, in which blood formation does not originate from healthy, but from mutated cells of origin (stem cells). The bone marrow of patients suffering from myelodysplastic syndromes is no longer able to produce fully mature and functional blood cells from these stem cells. In advanced stages of these diseases, more and more immature blood cells are produced. The blood formation process is therefore permanently disturbed and may also lead to acute myeloid leukemia (AML) in some patients at a later date.

Medigene AG (FSE: MDG1, ISIN DE000A1X3W00, Prime Standard, SDAX) is a publicly listed biotechnology company headquartered in Martinsried near Munich, Germany. The company is developing highly innovative immunotherapies to target various forms and stages of cancer. Medigene concentrates on the development of personalized T cell-based therapies with the focus on T cell-receptor modified T cells (TCR-Ts) and has associated projects currently in pre-clinical and clinical development. For more information, please visit View Source

This press release contains forward-looking statements representing the opinion of Medigene as of the date of this release. The actual results achieved by Medigene may differ significantly from the forward-looking statements made herein. Medigene is not bound to update any of these forward-looking statements. Medigene is a registered trademark of Medigene AG. This trademark may be owned or licensed in select locations only.